CARBOFLU · Chemoenzymatic synthesis of complex glycans to decipher the interactions between them and Influenza A virus
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-03-01 → 2019-02-28
- EU contribution
- €177,599
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Chemoenzymatic synthesis of complex glycans to decipher the interactions between them and Influenza A virus
Influenza A virus displays in majority in its surface two glycoproteins, Hemagglutinnin (HA) and Neuraminidase (NA). The virus mutate these two glycoproteins very fast what provides to it a via of escape from immune system. HA recognizes sialic acid containing glycans and NA cleaves these sialic acid moieties from the glycans. The affinity of HA for the glycans varies as the mutation occurs and the sialidase activity of NA also changes. In this project, our goal is to describe the chronological order of the mutation as well as to unravel wether there is any cooperation between the two envelope glycoproteins HA and NA. Influenza A virus is a major threat for the people all over the world. According to the World Health Organization (WHO), between 291,000 and 646,000 deaths worldwide are caused directly by the flu. Knowing more about the evolutionary pathway would increase the success rate of the new vaccines. a) Chemoenzymatic synthesis of a library of complex glycans. b) Interaction of the synthetic glycans with viral HA and NA. Conclusions Chemoenzymatic approach for the synthesis of glycans has been developed. The library of synthesized glycans has been used in binding affinity assays with HAs, in addition, the glycans has been employed to calculate the sialidase activity of the NAs.
Data: CORDIS, © European Union
Project objective
Influenza A virus has two major envelope glycoproteins: HA and neuraminidase (NA). HA binds to sialic acid moieties of glycoconjugates of the host respiratory cells to initiate infection, whereas NA facilitates the release of progeny viruses from infected cells by cleaving sialosides. It is well documented that binding preference is a major determinant of influenza virus host range and avian viruses preferentially bind Neu5Acα(2,3)Gal, whereas human viruses bind Neu5Acα(2,6)Gal. This difference in specificity represents a barrier for transmission of avian viruses into humans. Glycan arrays have been used to assess influenza A virus receptor specificity. However, the currently available glycan arrays contain only a fraction of the glycans found on human airway epithelial cells and cannot uncover glycan binding specificities. Thus, we propose to develop an array that contains glycans representative of the structures found in human airways, since it is a priority in order to understand the biology of influenza virus transmission and pathogenesis. In addition, it has been described that there are two pathways by which influenza virus enters cells. It is believed that some N-glycans serve as attachment factors for concentrating virus particles on the surface of the host cells. However, only specific cell surface proteins modified by appropriate N-glycans can facilitate cell entry. The elucidation of the influenza virus receptor structure will unveil the mechanism at molecular level by which virus enters the cell. To this end, we will develop an experiment, which allows us to identify glycoprotein receptors of flu virus using cell surface glycan editing. The full comprehension of multi-branched glycans, along with the identification of the glycoproteins receptors of influenza virus, will allow the development of new and more efficient glycan-based therapeutics.
Original text from CORDIS.
Participants
- UNIVERSITEIT UTRECHT · UtrechtCoordinatorNetherlands
Links
Data: CORDIS, © European Union